Cooperation between MYC and companion 8q genes in hepatocarcinogenesis.

Abstract

In this issue of Hepatology, Devanand Sarkar and coworkers report that AEG-1, a gene located at chromosomal region 8q22, cooperates with c-MYC (8q24) to induce a highly metastatic form of hepatocellular carcinoma (HCC) in transgenic mice.[1] The authors used the ALB (albumin) promoter to drive selective expression of these two 8q genes in mature hepatocytes, under conditions where MYC expression alone is sufficient to induce HCC, albeit a less-aggressive form without distant metastasis. Interestingly, expression of AEG-1 and MYC forms a positive feedback loop, in that each promotes the expression of the other, presumably playing a normal interacting role in liver development that is hijacked during hepatocarcinogenesis. Their oncogenic cooperation has an additional interesting feature in that the combination of AEG-1 and MYC, but neither gene alone, induces expression of maternally imprinted long noncoding RNAs (lncRNAs) RIAN and MEG3. The authors go on to show that expression of these lncRNAs play a functional role in AEG-1/MYC-induced malignancy.[1] As with the study of microRNAs a few years back, the study of lncRNAs is becoming increasingly central to current research in hepatocarcinogenesis.